Synthesis
The general procedure for the synthesis of methyl N-Boc-(2S,3R)-3-hydroxypyrrolidine-2-carboxylate from methyl (2S,3R)-N-Boc-3-benzoyloxy-2-pyrrolidinecarboxylate was as follows: methyl (2S,3R)-N-Boc-3-benzoyloxy-2-pyrrolidinecarboxylate (2.3 g, 6.58 mmol) was dissolved in methanol ( 20 mL) and cooled to 0°C in an ice bath. 1 mol/L aqueous potassium hydroxide solution (7.3 mL) was slowly added dropwise, the reaction temperature was kept at 0 °C and the reaction was stirred for 1 hour. Upon completion of the reaction, the pH was adjusted to acidic by adding 5% aqueous potassium bisulfate solution to the reaction mixture, followed by extraction with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography to afford the target product methyl N-Boc-(2S,3R)-3-hydroxypyrrolidine-2-carboxylate (1.55 g, 78% yield). The mass spectrum (ESI+) showed the molecular ion peak m/z 246 ([M+H]+, relative abundance 0.5%).
References
[1] Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7596 - 7599
[2] Patent: EP2876105, 2015, A1. Location in patent: Paragraph 1151; 1152
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 13, p. 3015 - 3025
[4] Patent: US2005/197359, 2005, A1. Location in patent: Page/Page column 17
